Intra-arterial administration of substance P (0.1-50 micrograms/kg) to the urinary bladder of the cat produced slow-onset and sustained bladder contractions, asynchronous firing of bladder postganglionic nerves, and facilitation of nicotinic transmission in bladder ganglia. Intracellular recording from bladder ganglia in vitro revealed that substance P depolarized ganglion cells and initiated burst of action potentials (maximal frequency 6-7 Hz). The ganglionic excitatory effect of substance P in situ was blocked by gamma-aminobutyric acid (2-20 micrograms/kg) and the substance P antagonist [D-Arg1,D-Pro2,D-Trp7.9,Leu11]substance P (0.5-20 micrograms/kg) but was not altered by atropine (10-100 micrograms/kg), hexamethonium (0.5-2 mg/kg), norepinephrine (2-20 micrograms/kg), or leucine enkephalin (0.5-20 micrograms/kg). The bladder contractions elicited by substance P were not blocked by atropine, hexamethonium, or [D-Arg1,D-Pro2,D-Trp7.9,Leu11]substance P (0.1-10 micrograms/kg) but were blocked by another substance P antagonist, [D-Pro2,D-Phe7,D-Trp9]substance P. These data indicate that substance P has a direct postsynaptic excitatory effect on neurons in the vesical parasympathetic ganglia and on bladder smooth muscle cells. The differential effects of substance P antagonists on the excitatory responses at these two sites indicate the responses were mediated by different types of tachykinin receptors.
The beneficial effects of meditation: contribution of the anterior cingulate and locus coeruleus